Methods and apparatus for performing renal neuromodulation via catheter apparatuses having inflatable balloons

ABSTRACT

Methods and apparatus are provided for non-continuous circumferential treatment of a body lumen. Apparatus may be positioned within a body lumen of a patient and may deliver energy at a first lengthwise and angular position to create a less-than-full circumferential treatment zone at the first position. The apparatus also may deliver energy at one or more additional lengthwise and angular positions within the body lumen to create less-than-full circumferential treatment zone(s) at the one or more additional positions that are offset lengthwise and angularly from the first treatment zone. Superimposition of the first treatment zone and the one or more additional treatment zones defines a non-continuous circumferential treatment zone without formation of a continuous circumferential lesion. Various embodiments of methods and apparatus for achieving such non-continuous circumferential treatment are provided.

REFERENCE TO RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 13/868,426, filed Apr. 23, 2013, which is a continuation ofU.S. patent application Ser. No. 13/620,173, filed Sep. 14, 2012, nowU.S. Pat. No. 8,444,640, which is a continuation of U.S. patentapplication Ser. No. 11/599,890, filed Nov. 14, 2006, now U.S. Pat. No.8,347,891, which is a continuation-in-part application of each of thefollowing:

(1) U.S. patent application Ser. No. 11/129,765, filed May 13, 2005, nowU.S. Pat. No. 7,653,438, which (a) claims the benefit of U.S.Provisional Patent Application Nos. 60/616,254, filed Oct. 5, 2004, and60/624,793, filed Nov. 2, 2004; and (b) is a continuation-in-part ofU.S. patent application Ser. No. 10/408,665, filed Apr. 8, 2003, nowU.S. Pat. No. 7,162,303, which claims the benefit of U.S. ProvisionalApplication Nos. 60/370,190 filed Apr. 8, 2002; 60/415,575, filed Oct.3, 2002; and 60/442,970, filed Jan. 29, 2003.

(2) U.S. patent application Ser. No. 11/189,563 filed Jul. 25, 2005, nowU.S. Pat. No. 8,145,316, which (a) is a continuation-in-part of U.S.patent application Ser. No. 11/129,765, filed May 13, 2005, now U.S.Pat. No. 7,653,438, which claims the benefit of U.S. Provisional PatentApplication Nos. 60/616,254, filed Oct. 5, 2004, and 60/624,793, filedNov. 2, 2004; and (b) is a continuation-in-part of U.S. patentapplication Ser. No. 10/900,199, filed Jul. 28, 2004, now U.S. Pat. No.6,978,174, which is a continuation-in-part of U.S. patent applicationSer. No. 10/408,665, filed Apr. 8, 2003, now U.S. Pat. No. 7,162,303,which claims the benefit of U.S. Provisional Application Nos. 60/370,190filed Apr. 8, 2002; 60/415,575, filed Oct. 3, 2002; and 60/442,970,filed Jan. 29, 2003.

All the foregoing applications and patents are incorporated herein byreference in their entireties.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

TECHNICAL FIELD

The present invention relates to methods and apparatus for performing anon-continuous circumferential treatment of a body lumen. Severalembodiments of such methods and apparatus are directed tocircumferential treatments of the body lumen that apply energy in one ormore discrete treatment areas to form one or more lesions that are notcontiguous or continuous about any complete circumference of across-section normal to a longitudinal axis of the body lumen.

BACKGROUND

Applicants have described methods and apparatus for treating a varietyof renal and cardio-renal diseases, such as heart failure, renaldisease, renal failure, hypertension, contrast nephropathy, arrhythmiaand myocardial infarction, by modulating neural fibers that contributeto renal function, e.g., denervating tissue containing the neural fibersthat contribute to renal function. This is expected to reduce renalsympathetic nervous activity, which increases removal of water andsodium from the body, and returns renin secretion to more normal levels.Normalized renin secretion causes blood vessels supplying the kidneys toassume a steady state level of dilation/constriction, which providesadequate renal blood flow. See, for example, Applicants' U.S. Pat. Nos.(a) 7,162,303; (b) 7,653,438; (c) 8,145,316; (d) 7,620,451; (e)7,617,005; and (f) 6,978,174. All of these applications and the patentare incorporated herein by reference in their entireties.

Applicants also have previously described methods and apparatus forintravascularly-induced neuromodulation or denervation of an innervatedblood vessel in a patient or any target neural fibers in proximity to ablood vessel, for example, to treat any neurological disorder or othermedical condition. Nerves in proximity to a blood vessel may innervatean effector organ or tissue. Intravascularly-induced neuromodulation ordenervation may be utilized to treat a host of neurological disorders orother medical conditions, including, but not limited to, theaforementioned conditions including heart failure and hypertension, aswell as pain and peripheral arterial occlusive disease (e.g., via painmitigation). The methods and apparatus may be used to modulate efferentor afferent nerve signals, as well as combinations of efferent andafferent nerve signals. See, for example, Applicants' co-pending U.S.Patent Application Publication No. US 2007/0129760, which isincorporated herein by reference in its entirety.

Although the foregoing methods are useful by themselves, one challengeof neuromodulation and/or denervation is sufficiently affecting theneural tissue from within the vessel. For example, intravascularneuromodulation should avoid increasing the risk of acute and/or latestenosis. Therefore, it would be desirable to provide methods andapparatus that further address these challenges.

BRIEF DESCRIPTION OF THE DRAWINGS

Several embodiments of the present invention will be apparent uponconsideration of the following detailed description, taken inconjunction with the accompanying drawings, in which like referencecharacters refer to like parts throughout, and in which:

FIG. 1 is a schematic isometric detail view showing a common location ofneural fibers proximate an artery.

FIGS. 2A-2J are schematic side views, partially in section, andcross-sectional views illustrating an example of methods and apparatusfor a non-continuous circumferential treatment of a body lumen.

FIG. 3 is a schematic side view, partially in section, illustrating analternative embodiment of the methods and apparatus of FIGS. 2.

FIG. 4 is a schematic side view, partially in section, illustratingfurther alternative methods and apparatus for non-continuouscircumferential treatments.

FIGS. 5A and 5B are schematic side views, partially in section,illustrating still further alternative methods and apparatus fornon-continuous circumferential treatments.

FIGS. 6A and 6B are schematic side views, partially in section,illustrating additional alternative methods and apparatus fornon-continuous circumferential treatments.

FIGS. 7A and 7B are schematic side views, partially in section,illustrating alternative embodiments of the apparatus and methods ofFIGS. 6.

FIG. 8 is a schematic side view, illustrating a non-continuouscircumferential treatment that is oblique to the lengthwise axis of thepatient's vasculature.

FIGS. 9A and 9B are schematic side views, partially in section,illustrating intravascular methods and apparatus for obliquecircumferential treatment.

FIGS. 10A and 10B are schematic side views, partially in section,illustrating extravascular embodiments of methods and apparatus fornon-continuous circumferential treatment of a body lumen, illustrativelyoblique circumferential treatment.

DETAILED DESCRIPTION

A. Overview

The applicants have discovered that it may be desirable to perform acircumferential treatment of a body lumen to positively affect a medicalcondition by applying energy to discrete zones that are non-continuousalong the complete circumference of a radial cross-section generallynormal to the lumen wall. For example, in the treatment of atrialfibrillation or other arrhythmia, a circumferential treatment may beachieved by forming a continuous circumferential lesion that iscontinuous completely about a normal cross-section of the pulmonary veinto disrupt aberrant electrical signals. In the treatment of heartfailure, a circumferential treatment may be achieved by forming asimilar continuous circumferential lesion that is continuous completelyabout a normal cross-section of a renal artery to reduce renalsympathetic neural activity. However, continuous circumferential lesionsthat extend continuously about a full 360° of the circumference of across-section normal to the body lumen or tissue in proximity to thebody lumen may increase a risk of acute and/or late stenosis formationwithin the blood vessel. Therefore, many of the embodiments describedbelow are directed to forming discrete, non-continuous lesions normal ofa lumen without adversely affecting the vessel.

Such non-continuous treatments may, for example, be conducted from anintravascular or intraluminal position, which can include treatmentutilizing elements passed from an intravascular location to anextravascular location, i.e., intra-to-extravascular treatment. However,it should be understood that extravascular treatment apparatus andmethods in accordance with the present invention also may be provided.

The treatments can be applied relative to nerves, including nervoustissue in the brain, or other target structures within or in proximityto a blood vessel or other body lumen that travel at least generallyparallel or along a lengthwise dimension of the blood vessel (bodylumen). The target structures can additionally or alternatively comprisea rotational orientation relative to the blood vessel (body lumen).Several disclosed embodiments of non-continuous circumferentialtreatments may reduce the risk of acute and/or late stenosis formationby treating neural matter along portions of multiple radial planes orcross-sections that are normal to, and spaced apart along, thelengthwise or longitudinal axis of the blood vessel (body lumen).

The treatment area at each radial plane or cross-section defines atreatment zone that is not completely continuous along a normalcircumference, i.e., defines a treatment zone without a continuouscircumferential lesion normal to the longitudinal axis. However,superimposition of the multiple treatment zones along the multipleradial planes or normal cross-sections defines a non-continuous,overlapping circumferential treatment zone along a lengthwise orlongitudinal segment of the blood vessel (body lumen). In someembodiments, this overlapping treatment zone may provide anon-continuous, but substantially fully circumferential treatmentwithout formation of a continuous circumferential lesion normal to thevessel (lumen). In other embodiments, the overlapping treatment zone mayprovide a non-continuous, partial circumferential treatment.

In this manner, a non-continuous circumferential treatment is performedover a lengthwise segment of the blood vessel (body lumen), as comparedto a continuous circumferential treatment at a single normalcross-section or radial plane. Target structures substantially travelingalong the lengthwise dimension of the blood vessel (body lumen) are thuscircumferentially affected in a non-continuous fashion without formationof the continuous circumferential lesion along any normal cross-sectionor radial plane of the blood vessel (body lumen). This may reduce a riskof acute or late stenosis formation within the blood vessel (bodylumen). A non-continuous circumferential treatment can thus comprise atreatment conducted at multiple positions about the lengthwise dimensionof a body lumen, wherein the treatment zone at any one lengthwiseposition does not comprise a continuous circumferential lesioncompletely about a radial plane or normal cross-section, but wherein asuperimposition of the treatment zones at all or some of the lengthwisepositions may define an overlapping circumferential treatment zone.

The non-continuous circumferential treatment optionally may be achievedvia apparatus positioned within a body lumen in proximity to targetneural fibers for application of energy to the target neural fibers. Thetreatment may be induced, for example, via electrical and/or magneticenergy application, via thermal energy application (either heating orcooling), via mechanical energy application, via chemical energyapplication, via nuclear or radiation energy application, via fluidenergy application, etc. Such treatment may be achieved, for example,via a thermal or non-thermal electric field, via a continuous or pulsedelectric field, via a stimulation electric field, via localized drugdelivery, via high intensity focused ultrasound, via thermal techniques,via athermal techniques, combinations thereof, etc. Such treatment may,for example, effectuate irreversible electroporation or electrofusion,necrosis and/or inducement of apoptosis, alteration of gene expression,action potential blockade or attenuation, changes in cytokineup-regulation, ablation and other conditions in target neural fibers.All or a part of the apparatus optionally may be passed through a wallof the body lumen to an extraluminal location in order to facilitate thetreatment. The body lumen may, for example, comprise a blood vessel, andthe apparatus may be positioned within the blood vessel via well-knownpercutaneous techniques.

Treatment may be achieved via either direct alteration of the targetstructures (e.g., target neural structures) or at least in part viaalteration of the vascular or other structures that support the targetstructures or surrounding tissue, such as arteries, arterioles,capillaries, veins or venules. In some embodiments, the treatment may beachieved via direct application of energy to the target or supportstructures. In other embodiments, the treatment may be achieved viaindirect generation and/or application of the energy, such as throughapplication of an electric field or of high-intensity focused ultrasoundthat causes resistive heating in the target or supporting structures.Alternative thermal techniques also may be utilized.

In some embodiments, methods and apparatus for real-time monitoring ofthe treatment and its effects on the target or support structures,and/or in non-target tissue, may be provided. Likewise, real-timemonitoring of the energy delivery apparatus may be provided. Power ortotal energy delivered, impedance and/or the temperature, or othercharacteristics of the target or non-target tissue, or of the apparatus,additionally or alternatively may be monitored.

When utilizing an electric field to achieve desired circumferentialtreatment, the electric field parameters may be altered and combined inany combination, as desired. Such parameters can include, but are notlimited to, frequency, voltage, power, field strength, pulse width,pulse duration, the shape of the pulse, the number of pulses and/or theinterval between pulses (e.g., duty cycle), etc. For example, suitablefield strengths can be up to about 10,000 V/cm, and may be eithercontinuous or pulsed. Suitable shapes of the electrical waveforminclude, for example, AC waveforms, sinusoidal waves, cosine waves,combinations of sine and cosine waves, DC waveforms, DC-shifted ACwaveforms, RF waveforms, microwaves, ultrasound, square waves,trapezoidal waves, exponentially-decaying waves, and combinationsthereof.

When utilizing a pulsed electric field, suitable pulse widths can be ofany desired interval, for example, up to about 1 second. The fieldincludes at least one pulse, and in many applications the field includesa plurality of pulses or is continuously applied, e.g., for up toseveral minutes. Suitable pulse intervals include, for example,intervals less than about 10 seconds. These parameters are provided assuitable examples and in no way should be considered limiting.

When utilizing thermal mechanisms to achieve the desired treatment,protective elements optionally may be provided to protect the non-targettissue, such as the smooth muscle cells, from thermal damage during thethermally-induced non-continuous circumferential treatment. For example,when heating target nerves or support structures, protective coolingelements, such as convective cooling elements, may be provided toprotect the non-target tissue. Likewise, when cooling target nerves orsupport structures, protective heating elements, such as convectiveheating elements, may be utilized to protect the non-target tissue.Thermal energy may be applied either directly or indirectly for a briefor a sustained period of time in order to achieve, for example, desiredneuromodulation or denervation. Feedback, such as sensed temperatureand/or impedance, along target or non-target tissue or along theapparatus, optionally may be used to control and monitor delivery of thethermal energy.

The non-target tissue optionally may be protected during, e.g., theneuromodulation or denervation, by utilizing blood flow as a conductiveand/or convective thermal sink that absorbs excess thermal energy (hotor cold). For example, when blood flow is not blocked, the circulatingblood may provide a relatively constant temperature medium for removingthe excess thermal energy from the non-target tissue during theprocedure. The non-target tissue additionally or alternatively may beprotected by focusing the thermal (or other) energy on the target orsupport structures, such that an intensity of the energy is insufficientto induce thermal damage in the non-target tissue distant from thetarget or support structures.

Additional and alternative methods and apparatus may be utilized toachieve a non-continuous circumferential treatment without formation ofa continuous circumferential lesion, as described hereinafter. To betterunderstand the structures of devices of the present invention and themethods of using such devices for non-continuous circumferentialtreatment, it is instructive to examine a common neurovascular anatomyin humans.

B. Neurovascular Anatomy Summary

FIG. 1 illustrates a common anatomical arrangement of neural structuresrelative to body lumens or vascular structures, typically arteries.Neural fibers N generally may extend longitudinally along the lengthwisedimension L of an artery A about a relatively small range of positionsalong the radial dimension r, often within the adventitia of the artery.The artery A has smooth muscle cells SMC that surround the arterialcircumference and generally spiral around the angular dimension θ of theartery, also within a relatively small range of positions along theradial dimension r. The smooth muscle cells of the artery accordinglyhave a lengthwise or longer dimension generally extending transverse(i.e., non-parallel) to the lengthwise dimension of the blood vessel.The misalignment of the lengthwise dimensions of the neural fibers andthe smooth muscle cells is defined as “cellular misalignment.”

The cellular misalignment of the nerves N and the smooth muscle cellsSMC may be exploited to selectively affect the nerve cells with reducedeffect on the smooth muscle cells. More specifically, a non-continuouscircumferential treatment may be achieved by superimposing treatmentsundertaken along multiple radial or cross-sectional planes of the arteryA that are separated along the lengthwise dimension L of the artery,rather than performing a continuous circumferential treatment along asingle radial plane or cross-section of the artery. In this manner, dueto the cellular misalignment, the lengthwise-oriented neural fibers mayexperience a full, non-continuous circumferential treatment, while theangularly-oriented smooth muscle cells may experience only a partialcircumferential treatment. Monitoring elements optionally may beutilized to assess an extent of treatment induced in the nerves and/orin the smooth muscle cells, as well as to adjust treatment parameters toachieve a desired effect.

C. Embodiments of Apparatus and Methods for Non-ContinuousCircumferential Treatment of a Body Lumen

FIGS. 2-7 and 9 illustrate examples of intravascular systems and methodsfor performing non-continuous circumferential treatments. The applicantshave described intravascular and intra-to-extravascular systems forneuromodulation or denervation, for example, in Applicants' U.S. Pat.Nos. 7,653,438 and 7,620,451, both of which have been incorporatedherein by reference. The applicants also have described extravascularsystems for neuromodulation or denervation (see, for example, U.S. Pat.No. 8,145,316, incorporated herein by reference), and it should beunderstood that non-continuous circumferential treatments may beperformed using extravascular (or extraluminal) systems, in addition tointravascular (intraluminal) or intra-to-extravascular(intra-to-extraluminal) systems (see FIGS. 10A and 10B). Applicants alsohave previously described thermal systems for neuromodulation ordenervation, for example, in Applicants' U.S. Pat. No. 7,617,665.

Referring now to FIGS. 2A-2J, the embodiment of an apparatus 300comprises a catheter 302 having an optional positioning element 304(e.g., a balloon, an expandable wire basket, other mechanical expanders,etc.) and expandable electrode element 306 positioned along the shaft ofthe catheter and illustratively located over the positioning element.The electrode element 306 can have one or more electrodes 307electrically coupled to a field generator 50 for delivery of an electricfield to the target neural fibers. In an alternative embodiment, one ormore of the electrode(s) 307 of the electrode element 306 may comprisePeltier electrodes for heating or cooling the target neural fibers tomodulate the fibers. The electrode(s) 307 optionally may be individuallyassignable and may be utilized in a bipolar fashion, and/or may beutilized in a monopolar fashion with an external ground pad attached tothe exterior of the patient.

The field generator 50, as well as any of the electrode embodimentsdescribed herein, may be utilized with any embodiment of the presentinvention for delivery of an electric field with desired fieldparameters. The field generator 50 can be external to the patient. Itshould be understood that electrodes of embodiments describedhereinafter may be electrically connected to the generator even thoughthe generator is not explicitly shown or described with each embodiment.Furthermore, the field generator optionally may be positioned internalto the patient, and the electrodes and/or the field generator optionallymay be temporarily or permanently implanted within the patient.

The positioning element 304 optionally may position or otherwise drivethe electrode(s) 307 into contact with the vessel wall. The positioningelement 304 may also comprise an impedance-altering element that altersthe impedance within the vessel during the therapy to direct theelectric field across the vessel wall. This may reduce an energyrequired to achieve desired neuromodulation or denervation and mayreduce a risk of injury to non-target tissue. Applicants have previouslydescribed use of an impedance-altering element, for example, inApplicants' U.S. Pat. No. 7,756,583, which is incorporated herein byreference in its entirety. When the positioning element 304 comprises aninflatable balloon, as in FIGS. 2A-J, the balloon may serve as both acentering and/or expansion element for the expandable electrode element306, and as an impedance-altering electrical insulator for directing anelectric field delivered via the electrode(s) 307 into or across thevessel wall for modulation of target neural fibers. Electricalinsulation provided by the element 304 may reduce the magnitude ofapplied energy or other parameters of the electric field necessary toachieve desired modulation of the target fibers, up to and includingfull denervation of tissue containing the target fibers.

Furthermore, element 304 optionally may be utilized as a thermalelement. For example, it may be inflated with a chilled fluid thatserves as a heat sink for removing heat from tissue that contacts theelement. Conversely, element 304 may be inflated with a warmed fluidthat heats tissue in contact with the element. The thermal fluid withinthe element optionally may be circulated and/or exchanged within thepositioning element 304 to facilitate more efficient conductive and/orconvective heat transfer. Thermal fluids also may be used to achievethermal neuromodulation via thermal cooling or heating mechanisms, asdescribed in greater detail herein below.

The electrode(s) 307 can be individual electrodes (i.e., independentcontacts), a segmented electrode with commonly connected contacts, or asingle continuous electrode. Furthermore, the electrode(s) 307 may beconfigured to provide a bipolar signal, or the electrode(s) 307 may beused together or individually in conjunction with a separate patientground pad for monopolar use. As an alternative or in addition toplacement of the electrode(s) 307 along the expandable electrode element306, as in FIG. 2, the electrode(s) 307 may be attached to thepositioning element 304 such that they contact the wall of the arteryupon expansion of the positioning element. In such a variation, theelectrode(s) may, for example, be affixed to the inside surface, outsidesurface or at least partially embedded within the wall of thepositioning element (see FIGS. 5A and 5B). In another embodiment, theelectrode(s) do not contact the vessel wall, and may be positioned atany desired location within the vessel.

The electrode(s) 307 or any other portion of the apparatus 300, such ascatheter 302 or element 304, additionally or alternatively may compriseone or more sensors, such as thermocouples 310, for monitoring thetemperature or other parameters of the target tissue, the non-targettissue, the electrodes, the positioning element and/or any other portionof the apparatus 300 or of the patient's anatomy. The treatment regimemay be controlled using the measured parameter(s) as feedback. Thisfeedback may be used, for example, to maintain the parameter(s) below adesired threshold, for example, a threshold that may cause injury to thenon-target tissues. Conversely, the feedback may be used to maintain theparameter(s) at or above a desired threshold, for example, a thresholdthat may induce a desired effect in the target tissues, such asneuromodulation of target neural fibers or denervation of tissuesinnervated by the target neural fibers. Furthermore, the feedback may beused to keep the parameter(s) within a range that will induce thedesired effect in the target tissues without injuring the non-targettissues to an unacceptable extent. Multiple parameters (or the same ormultiple parameters at multiple locations) optionally may be used ascontrol feedback for ensuring the desired effects while mitigating theundesired effects while mitigating the undesired effects.

As seen in FIG. 2A, the catheter 302 may be delivered to a treatmentsite within the artery A (or within a vein or any other vessel inproximity to target neural fibers) in a low profile deliveryconfiguration, for example, through the guide catheter or sheath 303.Alternatively, catheters may be positioned in multiple vessels forneuromodulation, e.g., within both an artery and a vein. Multi-vesseltechniques for electric field neuromodulation have been describedpreviously, for example, in Applicant's U.S. Pat. No. 7,853,333, whichis incorporated herein by reference in its entirety.

Once positioned within the vasculature as desired, the optionalpositioning element 304 may be expanded to display the electrode element306 and bring the electrode(s) 307 into contact with an interior wall ofthe vessel, as seen in FIG. 2B. An electric field then may be generatedby the field generator 50, transferred through the catheter 302 to theelectrode element 306 and the electrodes 307, and delivered via theelectrode(s) 307 across the wall of the artery. The electric fieldmodulates the activity along neural fibers within the wall of the arteryor in proximity to the artery, e.g., at least partially denervatestissue or organ(s) innervated by the neural fibers. This may beachieved, for example, via ablation or necrosis or via non-ablativeinjury or other changes to the target neural fibers or supportingstructures. The electric field also may induce electroporation in theneural fibers.

As seen in the cross-sectional view of FIG. 2C taken along the radialplane I-I of FIG. 2B, the apparatus 300 illustratively comprises fourelectrodes 307 equally spaced about the circumference of the electrodeelement 306 and the positioning element 304. As seen in FIG. 2D, whenutilized in a monopolar fashion in combination with an external ground(not shown; per se known), the circumferential segments treated by eachelectrode overlap to form discrete treatment zones TZ_(I) that are notcontinuous completely around the circumference of the artery in a radialplane normal to the vessel wall. As a result, there are discreteuntreated zones UZ_(I) about the circumference of the artery.

As seen in FIG. 2E, the electrode element 306 may be collapsed about theradial dimension r of the artery such that the electrodes 307 do notcontact the vessel wall, e.g., by collapsing the positioning element304. The electrode element 306 may be rotated about the angulardimension θ of the artery to angularly reposition the electrodes 307(best shown in FIG. 2G). This rotation may be achieved, for example, byangularly rotating the catheter 302. In FIG. 2E, the electrode elementillustratively has been rotated approximately 45° about the angulardimension of the artery. In the embodiment of apparatus 300 shown inFIGS. 2A-G, the electrodes are equally spaced about the circumference ofthe apparatus such that a 45° angular rotation repositions theelectrodes approximately halfway between the initial positions of theelectrodes shown in FIG. 2D.

In addition to angular repositioning of the electrodes, the electrodesmay be repositioned along the lengthwise or longitudinal dimension L ofthe artery, which is also shown in FIG. 2E as the longitudinal offsetbetween the electrodes 307 and the radial plane I-I. Such lengthwiserepositioning may occur before, after or concurrent with angularrepositioning of the electrodes. As seen in FIG. 2F, once repositionedin both the lengthwise and angular dimensions, the electrode element 306may be re-expanded about the radial dimension to contact the electrodes307 with the vessel wall. An electric field then may be delivered viathe angularly and lengthwise repositioned electrodes 307 along thenormal radial plane II-II.

In FIG. 2G, the treatment along radial plane II-II of FIG. 2F createstreatment zone TZ_(II) and untreated zone UZ_(II). As with the treatmentzone TZ_(I) of FIG. 2D, the treatment zone TZ_(II) of FIG. 2G is notcontinuous about the complete circumference of the artery. FIGS. 2H and2I allow comparison of the treatment zone TZ_(I) and the treatment zoneTZ_(II). The apparatus 300 is not shown in FIGS. 2H and 2I, e.g., theapparatus may have been removed from the patient to complete theprocedure.

As shown, the untreated zones UZ_(I) and UZ_(II) along the radial planesI-I and II-II, respectively, are angularly offset from one another aboutthe angular dimension θ of the artery (see FIG. 1). As seen in FIG. 2J,by superimposing the treatment zones TZ_(I) and TZ_(II), which arepositioned along different cross-sections or radial planes of the arteryA, a composite treatment zone TZ_(I-II) is formed that provides anon-continuous, yet substantially circumferential treatment over alengthwise segment of the artery. This superimposed treatment zonebeneficially does not create a continuous circumferential lesion alongany individual radial plane or cross-section normal to the artery, whichmay reduce a risk of acute or late stenosis formation, as compared toprevious circumferential treatments that create a continuouscircumferential lesion.

As discussed previously, non-continuous circumferential treatment bypositioning electrodes at different angular orientations along multiplelengthwise locations may preferentially affect anatomical structuresthat substantially propagate along the lengthwise dimension of theartery. Such anatomical structures can be neural fibers and/orstructures that support the neural fibers. Furthermore, such anon-continuous circumferential treatment may mitigate or reducepotentially undesirable effects induced in structures that propagateabout the angular dimension of the artery, such as smooth muscle cells.The angular or circumferential orientation of the smooth muscle cellsrelative to the artery may at least partially explain why continuouscircumferential lesions may increase a risk of acute or late stenosis.

Although in FIGS. 2A-J the electrode element 306 is expanded via thepositioning element 304, it should be understood that expandableelectrode elements or electrodes in accordance with the presentinvention additionally or alternatively may be configured to self-expandinto contact with the vessel wall. For example, the electrodes mayself-expand after removal of a sheath or a guide catheter 303constraining the electrodes in a reduced delivery configuration. Theelectrodes or electrode elements may, for example, be fabricated from(or coupled to) shape-memory elements that are configured toself-expand. Self-expanding embodiments optionally may be collapsed forretrieval from the patient by re-positioning of a constraining sheath orcatheter over the self-expanding elements. Optionally, the electrodeelement may be shapeable by a medical practitioner, e.g., in order toprovide a desired wall-contacting profile.

FIG. 3 illustrates an alternative embodiment of the apparatus 300 havinga self-expanding electrode element 306′. Positioning element 304 hasbeen removed from the apparatus. In use, the apparatus 300 is advancedto a treatment site within sheath or guide catheter 303. The sheath isremoved, and the element 306′ self-expands to bring the electrodes 307into contact with the vessel wall. Advantageously, blood continues toflow through the artery A during formation of treatment zone TZ_(I). Theelement 306′ then may be partially or completely collapsed (e.g., withinsheath 303), angularly rotated relative to the vessel, laterallyrepositioned relative to the vessel, and re-expanded into contact withthe vessel wall along a different radial plane or cross-section.Treatment may proceed at the new location and in the new angularlyorientation in the presence of blood flow, e.g., to form overlappingtreatment zone TZ_(II) that completes a non-continuous circumferentialtreatment zone TZ_(I-II) when superimposed with the treatment zoneTZ_(I). The element 306′ then may be re-collapsed, and the apparatus 300may be removed from the patient to complete the procedure.

Referring now to FIG. 4, it may be desirable to achieve a non-continuouscircumferential treatment without angular and/or lengthwiserepositioning of electrodes or other energy delivery elements. To thisend, in another embodiment an apparatus 400 comprises catheter 402having actively-expandable or self-expanding basket 404 having proximalelectrodes 406 and distal electrodes 408 spaced longitudinally apartfrom the proximal electrodes. The proximal electrodes 406 and distalelectrodes 408 are also spaced apart radially about the basket andelectrically coupled to the field generator 50 (see FIG. 2A). Theproximal electrodes 406 can be positioned along different struts orelements of the basket than the distal electrodes. The proximal anddistal electrodes are accordingly angularly and laterally offset fromone another.

The proximal electrodes may be operated independently of the distalelectrodes, and/or the proximal and distal electrodes all may beoperated at the same polarity, e.g., in a monopolar fashion as activeelectrodes in combination with an external ground. Alternatively oradditionally, the proximal electrodes may be utilized in a bipolarfashion with one another and/or the distal electrodes may be utilized ina bipolar fashion with one another. The proximal and distal electrodespreferably are not utilized together in a bipolar fashion. By treatingwith the distal electrodes 408, the treatment zone TZ_(I) of FIG. 2H maybe formed about the artery. Treating with the proximal electrodes 406may create the treatment zone TZ_(II) of FIG. 2I, which is angularlyoffset relative to the treatment zone TZ_(I). Superimposition of thetreatment zones TZ_(I) and TZ_(II) creates the non-continuouscircumferential treatment zone TZ_(I-II) over a lengthwise segment ofthe artery.

The proximal and distal electrodes optionally may be utilizedconcurrently to concurrently form the treatment zones TZ_(I) andTZ_(II). Alternatively, the electrodes may be operated sequentially inany desired order to sequentially form the treatment zones. As yetanother alternative, the treatment zones may be formed partially viaconcurrent treatment and partially via sequential treatment.

FIGS. 5A and 5B describe additional apparatus and methods fornon-continuous circumferential treatment without having to repositionelectrodes or other energy delivery elements. As seen in FIGS. 5A and5B, the apparatus 300 has an electrode element 306″ that comprises aflex circuit coupled to or positioned about the positioning element 304.The flex circuit is electrically coupled to the field generator 50 bywires that extend through or along the catheter 302 or by wireless. InFIG. 5A, the flex circuit comprises a collapsible cylinder positionedabout the positioning element 304. In FIG. 5B, the flex circuitcomprises individual electrical connections for each electrode 307,which may facilitate collapse of the flex circuit for delivery andretrieval. As with the electrodes of apparatus 400 of FIG. 4, theelectrodes 307 of FIG. 7 are spaced at multiple lengthwise positionsrelative to the positioning element and the blood vessel. The electrodesmay be operated as described previously to achieve a non-continuouscircumferential treatment. As the electrodes 307 illustratively arepositioned at three different lengthwise positions, the non-continuouscircumferential treatment may, for example, be formed viasuperimposition of three treatment zones (one at each lengthwiseposition within the blood vessel).

With any of the embodiments described herein, during delivery of theelectric field (or of other energy), blood within the vessel may act asa thermal sink (either hot or cold) for conductive and/or convectiveheat transfer for removing excess thermal energy from the non-targettissue (such as the interior wall of the vessel), thereby protecting thenon-target tissue. This effect may be enhanced when blood flow is notblocked during energy delivery, for example, as in the embodiments ofFIGS. 3 and 4 (it should be understood that a variation of theembodiments of FIG. 5 may provide for blood flow; for example, theelectrode(s) may be brought into contact with the vessel wall via anexpandable basket rather than via an inflatable balloon). Use of thepatient's blood as a thermal sink is expected to facilitate delivery oflonger or higher energy treatments with reduced risk of damage to thenon-target tissue, which may enhance the efficacy of the treatment atthe target tissue, for example, at target neural fibers.

In addition or as an alternative to utilizing the patient's blood as athermal sink, a thermal fluid (hot or cold) may be injected, infused orotherwise delivered into the vessel to remove excess thermal energy andprotect the non-target tissues. This method of using an injected thermalfluid to remove excess thermal energy from non-target tissues to protectthe non-target tissues from thermal injury during therapeutic treatmentof target tissues may be utilized in body lumens other than bloodvessels. The thermal fluid may, for example, comprise chilled or roomtemperature saline (e.g., saline at a temperature lower than thetemperature of the vessel wall during the therapy delivery). The thermalfluid may, for example, be injected through the device catheter orthrough a guide catheter. The thermal fluid injection may be in thepresence of blood flow or with flow temporarily occluded. Occlusion offlow in combination with thermal fluid delivery may facilitate bettercontrol over the heat transfer kinetics along the non-target tissues, aswell as optional injection of the fluid from a downstream location.

Referring now to FIGS. 6, another embodiment of the apparatus 300 isdescribed that comprises optional flow occlusion and thermal fluidinjection. The optional occlusion/positioning element 304 illustrativelyis coupled to the guide catheter 303, and the catheter 302 may berepositioned relative to the guide catheter to reposition theelectrode(s) 307, optionally without re-establishing flow through thevessel. In FIG. 6, the alternative electrode element 306′″ isself-expanding, and/or is shapeable (e.g., is formed from a springsteel) by a medical practitioner to provide a desired profile forpositioning of the electrode(s) 307 into contact with the vessel wall.

The catheter 302 may be advanced within the renal artery RA in a reducedprofile delivery configuration. Once properly positioned, the electrodeelement 306′″ may self-expand (or may be actively expanded) to bring theelectrode(s) 307 into contact with the vessel wall, for example, byremoving the electrode element from the lumen of the guide catheter. Theelement 304 also may be expanded (before, during or after expansion ofthe electrode element) in order to properly position the electrodewithin the vessel and/or to occlude blood flow within, e.g., the renalartery. An electric field, such as a monopolar electric field, may bedelivered via the electrode(s) 307, e.g., between the electrode(s) andan external ground (not shown; per se known). The electric field may,for example, comprise a pulsed or continuous RF electric field thatthermally induces neuromodulation (e.g., necrosis or ablation) in thetarget neural fibers. The therapy may be monitored and/or controlled,for example, via data collected with thermocouples or other sensors,e.g., impedance sensors.

In order to increase the power or duration of the treatment that may bedelivered without damaging non-target tissue of the vessel wall to anunacceptable extent, a thermal fluid infusate I may be injected, e.g.,through the guide catheter 303 to cool (heat) the non-target tissue,thereby mitigating damage to the non target tissue. The infusate may,for example, comprise chilled saline that removes excess thermal energy(hot or cold) from the wall of the vessel during thermal RF therapy.

Convective or other heat transfer between the non-target vessel walltissue and the infusate I may facilitate cooling (heating) of the vesselwall at a faster rate than cooling (heating) occurs at the target neuralfibers. This heat transfer rate discrepancy between the wall of thevessel and the target neural fibers may be utilized to modulate theneural fibers with reduced damage to the vessel wall. Furthermore, whenutilizing a pulsed therapy, the accelerated heat transfer at the wallrelative to the neural fibers may allow for relatively higher power orlonger duration therapies (as compared to continuous therapies), due tothe additional time between pulses for protective cooling at the vesselwall. Also, the interval between pulses may be used to monitor and/orcontrol effects of the therapy.

Referring now to FIG. 6B, treatment at additional angular and lengthwisepositions relative to the vessel wall may be achieved by rotation andlengthwise repositioning of the catheter 302. This may be repeated at asmany lengthwise and/or angular positions as desired by the medicalpractitioner. The treatment(s) at each individual lengthwise positionpreferably do not form a continuous circumferential lesion normal to thevessel wall, while superimposition of the treatments at multiple suchlengthwise positions preferably forms a non-continuous, partially orfully circumferential lesion, as described previously.

In the embodiment of the FIG. 6, the apparatus illustratively comprisesa single electrode 307. However, multiple such electrodes optionally maybe provided at multiple, angularly-offset positions, as in FIG. 7A. Thismay reduce the number of lengthwise positions where treatment needs tobe conducted in order to achieve the non-continuous, substantiallycircumferential treatment of the present invention. In addition or as analternative to angular offsetting, the electrodes optionally may beoffset lengthwise from one another, such that treatment at the multiplelengthwise positions may be achieved concurrently or sequentiallywithout necessitating lengthwise repositioning of the electrodes. FIG.7B illustrates an embodiment of apparatus 300 having multiple electrodesthat are offset from one another both angularly and lengthwise. In suchan embodiment, the relative angular and lengthwise positions of theelectrodes may be fixed or may be dynamically alterable by the medicalpractitioner.

As described herein, a continuous circumferential lesion is acircumferential lesion that is substantially continuous in a radialplane normal to the vessel or luminal wall. Conversely, a non-continuouscircumferential lesion may be non-continuous relative to a normal radialplane, but substantially continuous along an oblique plane of thevasculature that is not normal to the vessel wall. For example, as seenin dotted profile in FIG. 8, an oblique circumferential treatment OC maybe achieved within the patient's vasculature, e.g., the patient's renalartery RA, without formation of a continuous circumferential treatmentrelative to a normal radial plane of the vasculature. Thepreviously-described apparatus and methods of FIGS. 5 may, for example,form such an oblique circumferential treatment OC.

FIGS. 9A and 9B illustrate additional methods and apparatus forachieving such oblique circumferential treatments. In FIG. 9A, theapparatus 300 comprises a spiral or helical electrode element 307 thatcontacts the wall of the vasculature along one or more partial orcomplete oblique circumferences. The electrode element 307 may comprisea single continuous electrode over all or a portion of the spiral forformation of a continuous oblique treatment, and/or may comprisemultiple discrete electrodes positioned along the spiral, e.g., forformation of a non-continuous circumferential treatment relative to bothoblique and the normal planes of the vessel. Regardless of the form ofthe electrode element 307, the treatment zone(s) formed with theelectrode may form a non-continuous circumferential treatment relativeto the normal radial plane of the vasculature.

FIG. 9B illustrates an alternative embodiment of the apparatus andmethods of FIG. 9A, in which the electrode element 307 comprises adouble helix. This may facilitate formation of multiple, non-continuoustreatment zones along one or more normal radial planes of the vessel.Continuous or non-continuous oblique treatments also may be achieved,while non-continuous normal circumferential treatments are achieved viasuperimposition of treatment at multiple locations (either discrete orcontinuous) along a lengthwise segment of the vasculature.

Referring now to FIGS. 10A and 10B, extravascular variations aredescribed. FIG. 10A illustrates a percutaneous or transcutaneousextravascular variation having electrode(s) configured for temporaryplacement about the renal vasculature of the patient. FIG. 10Billustrates an implantable extravascular variation configured forprolonged placement within the patient. As will be apparent to those ofskill in the art, a composite extravascular variation also may beprovided having some elements configured for temporary placement andsome elements configured for prolonged placement. In one such variation,one or more electrodes may be implanted within the patient, and a pulsegenerator or battery charging unit, etc., may be placed external to thepatient and/or may be placed within the patient only temporarily duringtreatment, diagnostics, charging, etc.

The apparatus and methods of FIG. 10 illustratively are configured forformation of partially or completely continuous oblique circumferentialtreatments that are non-continuous relative to normal radial planes ofthe patient's vasculature. However, it should be understood thatalternative extravascular embodiments may comprise non-continuous normalcircumferential treatments that are non-continuous about both the normaland lengthwise dimensions of the vasculature, as opposed to just thenormal dimension, i.e., that are also non-continuous about the obliquesection. See, for example, the treatments defined by the apparatus andmethods of FIGS. 2-7.

In FIG. 10A, apparatus 500 comprises needle or trocar 503 that formspercutaneous access site P. Catheter 502 is advanced through the trocarinto proximity of the patient's renal artery RA. Electrode element 507spirals about the renal artery for formation of an obliquecircumferential treatment, as described with respect to FIG. 9A.Electrode element 507 is electrically coupled to field generator 50 fordelivery of a desired electrical treatment. The apparatus 500 optionallymay be removed from the patient, and the access site P closed, afterformation of the oblique circumferential treatment.

FIG. 10B illustrates an extravascular embodiment that is fullyimplantable and illustratively is configured for bilateral treatment ofnerves innervating both of the patient's kidney. It should be understoodthat any of the previously described embodiments also may be utilizedfor bilateral treatment, either concurrently or sequentially. Apparatus600 comprises first and second spiral electrode elements 607 a and 607 bthat spiral about the patient's renal arteries. The electrode elementsare electrically coupled to implantable field generator 650, e.g., viatunneled leads 652, for formation of the previously described obliquecircumferential treatment.

FIGS. 2-7 and 9-10 illustratively describe electrical methods andapparatus for circumferential treatment without formation of acontinuous circumferential lesion positioned normal to the lengthwiseaxis of the patient's vasculature. However, it should be understood thatalternative energy modalities, including magnetic, mechanical, thermal,chemical, nuclear/radiation, fluid, etc., may be utilized to achieve thedesired circumferential treatment without circumferential lesion.Furthermore, although FIGS. 2-7 and 9 illustratively comprise fullyintravascular positioning of the apparatus, it should be understood thatall or a portion of the apparatus in any of the embodiments may bepositioned extravascularly as in FIGS. 10, optionally via implantationand/or via an intra-to-extravascular approach.

Although preferred illustrative variations of the present invention aredescribed above, it will be apparent to those skilled in the art thatvarious changes and modifications may be made thereto without departingfrom the invention. For example, although in the described embodimentsof FIGS. 2-4 non-continuous circumferential treatment is achieved viasuperimposition of treatment at two locations, it should be understoodthat treatment at more than two locations may be superimposed to achievethe circumferential treatment, as described with respect to FIGS. 5A and5B. Furthermore, although in the described embodiments the methods areconducted in a blood vessel, it should be understood that treatmentalternatively may be conducted in other body lumens. It is intended inthe appended claims to cover all such changes and modifications thatfall within the true spirit and scope of the invention.

We claim:
 1. A method of performing renal neuromodulation, the methodcomprising: intravascularly positioning a catheter in a reduced profiledelivery configuration within a renal blood vessel and proximate to arenal nerve of a human patient; transforming the catheter from thedelivery configuration to a treatment configuration, wherein a distalballoon is expanded to place a plurality of electrodes arrangedthereabout in a staggered configuration proximate to the renal nerve,wherein the plurality of electrodes comprises (a) a first electrodehaving a first pair of bipolar contacts and (b) a second electrodehaving a second pair of bipolar contacts; and modulating the renal nerveby— selectively energizing the first electrode to produce a firsttreatment zone along the renal blood vessel, and selectively energizingthe second electrode to produce a second treatment zone along the renalblood vessel.
 2. The method of claim 1 wherein selectively energizingthe first and second electrodes to produce the first and secondtreatment zones, respectively, occurs without repositioning thecatheter.
 3. The method of claim 1 wherein intravascularly positioningthe catheter comprises delivering the catheter over a guidewire.
 4. Themethod of claim 1 wherein the first and second electrodes are staggeredsuch that the first treatment zone and the second treatment zone do notoverlap.
 5. The method of claim 1 wherein selectively energizing thefirst electrode to produce the first treatment zone and selectivelyenergizing the second electrode to produce the second treatment zoneoccur in sequence.
 6. The method of claim 1 wherein selectivelyenergizing the first electrode to produce the first treatment zone andselectively energizing the second electrode to produce the secondtreatment zone occur concurrently.
 7. The method of claim 1 wherein thefirst electrode and the second electrode are parts of a flex circuit ona surface of the balloon.
 8. The method of claim 7 wherein the flexcircuit terminates proximally of a distal end portion of the balloon. 9.The method of claim 1 wherein the balloon is configured to bring thefirst electrode and the second electrode into apposition with an innerwall of the renal blood vessel when the catheter is in the deployedconfiguration.
 10. The method of claim 1 wherein the balloon isconfigured to block fluid flow within the renal blood vessel duringenergy delivery.
 11. The method of claim 1 wherein the plurality ofelectrodes further comprises a third electrode having a third pair ofbipolar contacts and a fourth electrode having a fourth pair of bipolarcontacts, and wherein modulating the renal nerve further comprises:selectively energizing the third electrode to produce a third treatmentzone along the renal blood vessel; and selectively energizing the fourthelectrode to produce a fourth treatment zone along the renal bloodvessel, wherein each of the plurality of electrodes is configured todeliver thermal energy to less than a full circumference of the renalblood vessel.
 12. The method of claim 1, further comprising monitoring aparameter of the balloon, electrodes, and/or tissue proximate the renalnerve within the patient during therapy.
 13. The method of claim 12wherein monitoring a parameter comprises monitoring temperature of theballoon, electrodes, and/or tissue, and wherein the method furthercomprises maintaining a desired temperature throughout therapy.
 14. Themethod of claim 12, further comprising altering treatment in response tothe monitored parameter.
 15. The method of claim 14 wherein alteringtreatment comprises deactivating an electrode that the monitoredparameter indicates is not in apposition with an inner wall of the renalblood vessel.
 16. The method of claim 1 wherein modulating the renalnerve comprises ablating the renal nerve of the patient via thermalenergy from the first and second electrodes.
 17. The method of claim 1wherein modulating the renal nerve comprises partially ablating therenal nerve of the patient via thermal energy from the first and secondelectrodes.
 18. The method of claim 1 wherein modulating the renal nervecomprises at least partially blocking neural traffic to and/or from akidney of the patient.
 19. The method of claim 1, further comprisingrepositioning the catheter and distal balloon within the renal bloodvessel of the patient after producing the first and second treatmentzones, and wherein, after repositioning, the method further comprisesselectively energizing the first and second electrodes to produce thirdand fourth treatment zones, respectively, along the renal blood vessel.20. The method of claim 1 wherein intravascularly positioning a catheterwithin a renal blood vessel comprises positioning the catheter within arenal artery of the patient.
 21. A method of performing renalneuromodulation, the method comprising: intravascularly delivering acatheter over a guidewire in a low profile delivery configuration to avicinity of a renal nerve of a human patient; transforming the catheterfrom the delivery configuration to a treatment configuration, wherein adistal balloon is expanded to place a plurality of electrodes arrangedthereabout in a staggered configuration into contact with an inner wallof a renal blood vessel of the patient, and wherein each electrodecomprises a pair of bipolar contacts; selectively energizing a firstelectrode to produce a first treatment zone along the renal bloodvessel; and selectively energizing a second electrode to produce asecond treatment zone along the renal blood vessel, wherein selectivelyenergizing the first and second electrodes modulates the renal nerve toreduce renal sympathetic nerve activity of the patient.
 22. The methodof claim 21 wherein the first and second electrodes are staggered suchthat the first treatment zone and second treatment zone do not overlap.23. The method of claim 21 wherein the first and second electrodes arestaggered such that the first treatment zone and second treatment zoneoverlap.
 24. The method of claim 21 wherein selectively energizing thefirst electrode and selectively energizing the second electrode occursimultaneously.
 25. The method of claim 21 wherein, when the catheter isin the treatment configuration, the balloon occludes the renal bloodvessel.
 26. The method of claim 21 wherein modulating the renal nerve toreduce renal sympathetic nerve activity comprises thermally modulatingafferent and efferent renal nerves of the patient.